Common rules guide comparisons of speed and direction of motion in the dorsolateral prefrontal cortex

Abstract

When a monkey needs to decide whether motion direction of one stimulus is the same or different as that of another held in working memory, neurons in dorsolateral prefrontal cortex (DLPFC) faithfully represent the motion directions being evaluated and contribute to their comparison. Here, we examined whether DLPFC neurons are more generally involved in other types of sensory comparisons. Such involvement would support the existence of generalized sensory comparison mechanisms within DLPFC, shedding light on top-down influences this region is likely to provide to the upstream sensory neurons during comparison tasks. We recorded activity of individual neurons in the DLPFC while monkeys performed a memory-guided decision task in which the important dimension was the speed of two sequentially presented moving random-dot stimuli. We found that many neurons, both narrow-spiking putative local interneurons and broad-spiking putative pyramidal output cells, were speed-selective, with tuning reminiscent of that observed in the motion processing middle temporal (MT) cortical area. Throughout the delay, broad-spiking neurons were more active, showing anticipatory rate modulation and transient periods of speed selectivity. During the comparison stimulus, responses of both cell types were modulated by the speed of the first stimulus, and their activity was highly predictive of the animals' behavioral report. These results are similar to those found for comparisons of motion direction, suggesting the existence of generalized neural mechanisms in the DLPFC subserving the comparison of sensory signals.

Figure 1.

Behavioral task; performance; recording sites. A, Speed discrimination task. Animals reported whether coherently moving random-dot stimuli presented during S1 and S2 stimuli moved at the same or different speeds by pressing one of the two response buttons. On each trial, a stimulus moving at base speed (2 or 4°/s), indicated by shorter arrows, was compared with a stimulus moving either at the same speed (two bottom rows) or at a higher speed (two top rows). The base and the faster speeds could appear at random either during S1 or S2. On trials with S1 and S2 moving at the same speed, stimuli moved either at base speeds (third row) or at any of the comparison speeds (bottom row). These two types of trials (same and different) were randomly interleaved, and comparison speeds were chosen to bracket the animal's threshold. B, Average psychometric functions for the two monkeys, based on 30,142 trials collected during 150 recording sessions. The average performance of each animal is plotted as a function of speed differences between S1 and S2, expressed as a Weber fraction (ΔV/V), where ΔV is speed increment and V is base speed. C, Locations of all task-related neurons recorded in each animal indicated by triangles (Monkey 1) and circles (Monkey 2). Recordings were clustered between the principal and the arcuate sulcus, with the larger proportion of neurons located in the ventral region.

Figure 2.

Speed-selective activity during speed discrimination task. A, B, Spike density functions for an example NS putative interneuron (A) and BS putative pyramidal (B) neuron. Spike trains were convolved with a 20 ms Gaussian to show activity. Different colored lines represent average firing rates for each speed. Both neurons were DS. The data are shown for S1 and S2 moving in the neuron's preferred direction. C, D, Response tuning to speeds presented during S1 (left) and S2 (right) for the NS (C) and BS (D) cells shown in A and B. Responses were computed for activity measured during 50–500 ms after stimulus offset. The curve fitting the data is the best-fit log-Gaussian function for each neuron (Materials and Methods).

Figure 3.

Response selectivity of NS and BS neurons for stimulus speed. A, Average normalized response to S1 for the most preferred (solid line) and least preferred (broken line) stimulus speeds for all recorded NS (left plot, n = 35) and BS (right plot, n = 97). B, Average speed selectivity (AROC) for NS and BS neurons computed by comparing responses shown in A. C, Distribution of AROC for all NS (top) and BS (bottom) neurons shown in B. AROCs were calculated for the 50–550 ms period after the onset of S1. Neurons with significant selectivity (p < 0.05) are indicated by filled colored bars. The distributions show stronger average selectivity in NS neurons (NS = 0.70 ± 0.004, BS = 0.65 ± 0.007, p = 0.036, Mann–Whitney U test).

Figure 4.

Speed tuning functions. A, Distribution of R² values for log-Gaussian fits of all significantly speed-selective NS and BS neurons (n = 95). R² > 0.6 was defined as well fit (n = 57), whereas R² < 0.6 was labeled as not well fit (n = 38). B, Types of speed tuning encountered in the PFC. Neurons with low pass (n = 26), bandpass (n = 13), and high-pass (n = 18) speed tuning. Only cells that were well fit by the log-Gaussian function (R² > 0.6) were used for this analysis. Individual data points represent average responses to each speed recorded during the period of 50–500 ms after S1 onset. Black lines indicate the average fit for all low-pass, bandpass, and high-pass neurons.

Figure 5.

Reduced speed selectivity during passive fixation. A, Stimulus conditions during speed discrimination and passive fixation. Sensory conditions during the two tasks were identical, except for different fixation targets (▴ vs X). During the passive fixation task, the monkeys were rewarded at the end of each trial and were not required to press response buttons. B, Speed selectivity of responses to S1 (n = 30) and S2 (n = 33) recorded during the two tasks. Thick black lines along x-axis indicate times of significant differences between the two curves (p < 0.05, Wilcoxon sign-rank test). C, Selectivity of individual NS and BS neurons during the two tasks. Each data point represents activity recorded during the last 100 ms of the response (400–500 ms). Speed selectivity was weaker on passive fixation trials during S1 (p < 0.012) and S2 (p < 0.002). D, Comparison of task effects on selectivity during S1 and S2. Task effect was computed as the difference in AROC values during the two tasks (AROC_passive − AROC_speed). Negative values indicate a decrease in selectivity during passive fixation. E, Cell-by-cell comparison of task effects during S1 and S2. Each data point represents task effect measured at 100–300 ms after stimulus onset. During passive fixation, selectivity loss was greater during S2 (p = 0.0175, Wilcoxon sign-rank test).

Figure 6.

Time-dependent modulation of delay activity. A, Incidence of neurons with significant delay activity. The thick black line indicates the period of significant difference between NS and BS (χ² test, p < 0.05). The dashed line at 5% indicates the level of significance expected by chance. NS cells, n = 37; BS, n = 113. B, Time-dependent modulation of delay activity for BS (top) and NS (bottom) neurons. DMI = (activity late delay) − activity middle delay)/(activity late delay + activity middle delay). Late delay, last 200 ms of delay; middle delay, 200 ms centered at 1250 ms. Values > 0 indicate higher activity in late delay; values < 0 indicate lower activity in late delay. Filled colored bars, cells with significant modulation (Wilcoxon sign-rank test, p < 0.01); gray bars, cells with no delay modulation. BS neurons showed stronger delay modulation (NS, DMI = 0.126 ± 0.02; BS, DMI = 0.22 ± 0.02; Mann–Whitney U test, p = 0.011).

Figure 7.

Reduced modulation of delay activity during passive fixation. A, Comparison of delay activity during the speed and the passive fixation tasks. Only cells with significant increase in activity during the speed task were used (n = 21). B, Cell-by-cell comparison of DMIs (see Fig. 6 legend) for all NS (n = 6) and BS (n = 24) neurons in both tasks. All negative DMIs (squares) have been reflected >0 to facilitate the comparisons with the positive DMI (circles). Delay modulation was greatly reduced during passive fixation (p = 0.00009, Wilcoxon sign-rank test), with no significant difference in the size of effect between raising or decreasing activity types (p = 0.82, Mann–Whitney U test).

Figure 8.

Speed-selective activity during the delay. A, Speed selectivity of individual BS (n = 113) and NS (n = 37) neurons during S1 and the delay quantified by ROC analysis. Scale bar on the right shows ROC values (most preferred speed, blue; least preferred speed, red. The data were sorted by the selectivity during S1 (50–550 ms). B, Durations of speed-selective epochs for NS and BS neurons during the delay. C, Average speed selectivity for NS and BS neurons. Baseline AROC was defined by the average AROC during the last 500 ms of fixation. The black line along x-axis indicates period of significant difference between BS and NS neurons (Mann–Whitney U test, p < 0.05). D, Relationship between speed selectivity of individual neurons during S1 and during the delay. Only cells with significant selectivity during S1 were included in this analysis (NS cells, N = 17; BS, N = 43; 50–550 ms, p < 0.05, Mann–Whitney U test). Selectivity of each neuron during S1 is plotted against its selectivity in early (500–1000 ms), middle (1000–1500 ms), and late (1500–2000 ms) delay. Filled and open symbols indicate selective (p < 0.05) and nonselective (p > 0.05) neurons, respectively, during each period of the delay. AROC > 0.5 indicates selectivity in the same sign as S1; AROC < 0.5 indicates selectivity of opposite sign to S1. Column plots to the right of each scatterplot show the incidence of neurons with selectivity of the same (top) or opposite (bottom) sign as that in S1. Middle columns show the incidence of nonselective cells. Note the increasing number of neurons in the middle columns with time in delay.

Figure 9.

Speed-selective delay activity is weakened during passive fixation. A, Average delay selectivity during the speed and the passive fixation tasks. Each data point represents average activity of 27 BS and 7 NS neurons during three consecutive 500 ms periods of the delay. B, Speed selectivity of individual neurons contributing to data shown in A. NS and BS neurons with significant activity in the speed task (●), and in the passive task alone (■) are shown separately. ○, neurons with no significant selectivity in either task. Selectivity was greater during the speed task throughout the delay (early: p = 0.005; middle: p = 0.003; late: p = 0.0001, Wilcoxon sign-rank test).

Figure 10.

Modulation of S2 responses by the preceding speed. A, Diagram of the two types of trials used to evaluate CEs. Longer and shorter arrows indicate faster and slower speeds, respectively. B, CEs in individual neurons quantified with ROC analysis (BS = 103, NS = 33). AROC values > 0.5 (cooler colors) indicate higher activity on S-trials; AROC values < 0.5 (warmer colors) indicate stronger activity on D-trials. Neurons were sorted by timing and sign of their CEs. C, Average CEs for S > D (n = 51) and D > S (n = 28) cells during S2 and post-S2 periods. Shadings indicate ± SEM. Period of significant effect is indicated by a thick horizontal line (red for S > D; blue for D > S). D, Distribution of S > D and D > S effects contributing to the average data shown in C. E, Distribution of timing of maximal CEs for S > D (blue) and D > S (red) neurons. Mean latencies: S > D cells, 506 ± 47 ms; D > S cells, 458 ± 53 ms. F, Relationship between the CE (y-axis) and speed difference (x-axis). Each data point represents maximal CE at a given speed difference for each neuron. Both cell types showed a decreased CE with smaller differences in speed.

Figure 11.

Attenuation of comparison effects during passive fixation. A, Average comparison effects during the speed and the passive fixation tasks computed for cells with sufficient number of trials during the two tasks (NS = 4, BS = 17). Trial-type preference was based on S2 responses during the speed task (see Materials and Methods). B, Cell-by-cell comparison effects recorded during the two tasks. Each data point represents activity recorded during 400–600 ms after the onset of S2. The effects were weaker during the passive task (Wilcoxon sign-rank test, p = 0.004).

Figure 12.

Representation of “Same” and “Different” effects across tasks. A, Diagram of the two types of trials used to evaluate comparison effects during the speed (top) and direction (bottom) discrimination tasks. The two tasks were run in separate blocks. B, Correlation between comparison effects calculated in both tasks for all neurons (N = 70). Neurons are color-coded for trial-type preference exhibited during the speed discrimination task (S > D=blue, D > S=red, S=D, gray). The data show a strong correlation between trial type preference of individual neurons during the two tasks (R² = 0.604, Pearson's correlation, p = 3.0 × 10⁻⁸).

Figure 13.

Activity during and after S2 predicts upcoming perceptual report. A, CP of neurons with higher activity before “different reports” (n = 27) and higher activity before “same reports” (n = 31). Thick colored lines along the x-axis indicate period of significance (Mann–Whitney U test, p < 0.05). Shadings represent ± SEM. B, Distribution of CP values contributing to the data plotted in A. CPs were computed for the period of 300–800 ms after S2 onset. C, Time of maximal CP for neurons contributing to CP curves shown in A. Average maximal CP times for “same” and “different” reports were similar (“same,” 526 ms; and “different,” 567 ms; p = 0.39). D, Incidence of CE and CP signals co-occurring in the same neurons (CP and CE, n = 32; CE, n = 29; CP, n = 19; no effect, n = 28).

Figure 14.

Relationship between comparison and choice-related activity. A, CEs (solid lines) and CP (broken lines) in S > D neurons (n = 23) and D > S neurons (n = 9). Only neurons with co-occurring CE and CP (see Fig. 13D) were used. B, Times of maximal CP and CE for individual neurons. Note that the time of maximal CP trailed the time of maximal CE (p = 0.001, Wilcoxon sign-rank test). C, Correlation between CE and CP for individual S > D and D > S cells at 300–500 ms (p = 2.0 × 10⁻⁵, R² = 0.43, Pearson's correlation) and at 900–1100 ms (p = 8.0 × 10–6, R² = 0.48, Pearson's correlation) after S2 onset. D, Coefficient of correlation between CE and CP, computed across time (late delay, during S2 and post-S2).